First preparation of enantiopure indane monomer, (S)- (-)- and (R)-(+)-2,3-dihydro-3-(4′-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol, via a unique enantio- and regioselective enzymatic kinetic resolution

Compound 1, (2,3-dihydro-3- (4'-hydroxyphenyl)-1,1,3-trimethyl-1H-inden-5-ol), a highly valuable monomer was prepared for the first time into its two enantiomerically pure forms via enzyme catalyzed kinetic resolution of corresponding 1-diesters. Hydrolysis of 1-dipentanoate catalyzed by lipase from Chromobacterium viscosum (CVL) is highly regioselective (38:1) between two phenyl groups and highly enantioselective (E = 48) toward a remote quaternary chiral center (five bonds), yielding (S)-(-)-1-4-monopentanoate and unreacted (R)-(+)-1-dipentanoate in high yield and excellent ee. Unlike other hydrolase-catalyzed reactions, the CVL-catalyzed reaction does not proceed to sequential hydrolysis of (S)-(-)-1-4'-monopentanoate to (S)-(-)-1, showing that the reaction is also highly chemical selective between 1-diester and 1-monoester. The structural preference of the reaction was clearly determined by H-1 and COSY NMR. The absolute configuration of the nonreacted (R)-(+)-1-dipentanoate was determined consistently by circular dichroism and X-ray crystallography after being chemically transformed to (R)-(+)-1 and derivatives. Surprisingly, CVL favors the carbonyl group on the more substituted phenol, which has more steric hindrance, shorter bond length (1.39 Angstrom compared to 1.41 Angstrom on less substituted phenyl), and was believed to be the less favored group. In brief, in this reaction, the more substituted phenol group is preferred. (S)-enantiomer is:preferred. l-Diesters are substrates while corresponding 1-monoesters are not. The unique feature of CVL provides a simple access to enantiopure dial 1, corresponding 1-monoestesrs, 1-homodiesters, as well as 1-mixed diesters.